乙肝病毒（HBV）感染的慢性化与机体特异性细胞毒T淋巴细胞（CTL）免疫应答低下有关。我们的前期研究显示，慢性HBV感染者体内树突细胞（DC）的蛋白酶体功能受抑，而三肽基肽酶Ⅱ(TPPⅡ)作为细胞内普遍存在的大分子蛋白水解酶，对蛋白酶体的功能有补充和代偿作用，在降解病毒相关蛋白、MHCⅠ类分子提呈以及诱导特异性细胞免疫过程中起着重要作用。本课题拟构建N端突变的多聚谷氨酸HBcAg非复制型重组腺病毒，转染DC，利用TPPⅡ将HBcAg降解成最适于提呈的短肽，通过MHC Ⅰ类抗原加工提呈途径提呈，诱导HBV特异性CTL反应，并对JAK/STAT通路下游转录因子的表达进行研究，以期进一步阐明JAK/STAT通路与TPPⅡ作用下HBcAg诱导CTL的相关性。本课题将阐明N端突变的多聚谷氨酸HBcAg在TPPⅡ作用下诱导HBV特异性CTL反应的效果及机制，为慢性乙型肝炎的抗病毒治疗提供新的策略。

Chronic hepatitis B virus (HBV) infection is related to weak specific cellular immune response of host to HBV. Our previous studies have shown that the function of proteasome of dendritic cells (DC) in patient with chronic HBV infection is inhibitted.Three dipeptidyl peptidase Ⅱ (TPP Ⅱ) as an intracellular macromolecules proteolytic enzymes, plays an important role of complementary and compensatory for proteasome in the viral protein degradation, MHC class I antigen presentation and inducing specific cellular immune in vivo. On the basis of preliminary studies, we intend to immunize HBV transgenic mice with DCs transfected with non-replication recombindant adenovirus encoding N-terminal mutant polyglutamate HBcAg gene, in order to make HBcAg be degradated by TPP Ⅱ to become the epitope peptide suitable for presenting by MHC class I antigen presenting pathway, then, HBV-specific CTL responses of the body can be effectively stimulated. on the other hand, we intend to investigate the expression of JAK/STAT pathways downstream transcription factors in order to determine the correlation between Jak/STAT pathway and CTL responses induced by N-terminal mutant polyglutamine HBcAg degraded by TPP Ⅱ. The aim of this study is to investigate the mechanism and capacity of DCs induced with N-terminal mutant polyglutamate HBcAg mediated by adenovirus vector to stimulate lymphocytes proliferation and generate stronger HBV-specific CTL responses，the results may be helpful in seeking novel approaches to the control of persistent HBV infection,and provide a new idea and experimental basis of immune therapy for chronic HBV infection.